Down‐Regulation of Hepatic Stearoyl‐CoA Desaturase‐1 Expression by Fucoxanthin via Leptin Signaling in Diabetic/Obese KK‐A^y Mice

Abstract

Stearoyl-coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. Recently, SCD1 down-regulation has been implicated in the prevention of obesity, and the improvement of insulin and leptin sensitivity. In this study, we examined the effect of fucoxanthin, a marine carotenoid, on hepatic SCD1 in obese mouse models of hyperleptinemia KK-A(y) and leptin-deficiency ob/ob. In KK-A(y) mice, providing a diet containing 0.2 % fucoxanthin for 2 weeks markedly suppressed SCD1 mRNA and protein expressions in the liver. The fatty acid composition of liver lipids was also affected by an observed decrease in the ratio of oleic acid to stearic acid. Furthermore, serum leptin levels were significantly decreased in hyperleptinemia KK-A(y) mice after 2 weeks of fucoxanthin feeding. However, the suppressive effects of fucoxanthin on hepatic SCD1 and body weight gain were not observed in ob/ob mice. These results show that fucoxanthin down-regulates SCD1 expression and alters fatty acid composition of the liver via regulation of leptin signaling in hyperleptinemia KK-A(y) mice but not in leptin-deficient ob/ob mice.

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“…Down-regulation of hepatic SCD1 expression has been observed through leptin signalling (22). Beppu et al (22) indicated that suppression of the SCD index and SCD1 expression in the liver occurred in parallel with a lower serum leptin level as did the present results and our previous study (5).…”

“…It has been indicated that the serum TAG level was suppressed to around half by the pair-feeding and lower food intake in comparison with the case of the ad libitum feeding study (5). Down-regulation of hepatic SCD1 expression has been observed through leptin signalling (22). Beppu et al (22) indicated that suppression of the SCD index and SCD1 expression in the liver occurred in parallel with a lower serum leptin level as did the present results and our previous study (5).…”

Fucoxanthin and lipid metabolism: A minireview

“…Indeed, in diabetic/obese KK-A y mice, FX (0.2% for 4 weeks) significantly decreased stearoyl-coenzyme A desaturase-1 mRNA and protein expression, body weight gain and serum leptin levels, as well as the hepatic oleic/stearic acid ratio [35]. The role of leptin in mediating the anti-obese effects of FX gained further support from the observation that they were completely abrogated in leptin-deficient ob/ob mice [35]. The FX-induced increase in expression of β3-adrenergic receptor in WAT could be an addition factor for enhancing lipogenesis in obese mice [34].…”

“…Its downregulation prevents obesity and improves sensitivity to insulin and leptin. Indeed, in diabetic/obese KK-A y mice, FX (0.2% for 4 weeks) significantly decreased stearoyl-coenzyme A desaturase-1 mRNA and protein expression, body weight gain and serum leptin levels, as well as the hepatic oleic/stearic acid ratio [35]. The role of leptin in mediating the anti-obese effects of FX gained further support from the observation that they were completely abrogated in leptin-deficient ob/ob mice [35].…”

Fucoxanthin Enhances Chain Elongation and Desaturation of Alpha‐Linolenic Acid in HepG2 Cells

“…Moreover, the last step of ALA to DHA conversion, C24:6n-3 to DHA, involved a peroxisomal β-oxidation which has been known to be regulated by PPARα. Woo et al (2010) reported that FX supplementation significantly increased mRNA of PPARα and its target gene acyl-CoA oxidase-1 (ACOX-1) in high fat diet-fed C57BL/6 N mice [27]. Beppu (2012) reported increased SREBP-1 and SREBP-2 protein in the liver of KK-A y mice fed the FX-containing diet [28].…”